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Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease.

ABSTRACT: Whether the clinical trial treatment effect of urate-lowering therapy (ULT) in patient with chronic kidney disease (CKD) is generalizable to real-word settings is unclear. This study aimed to compare febuxostat with allopurinol for uric acid reduction and renal protection in patients with CKD. Adult CKD patients newly treated with ULT were identified using electronic health records from 2010 to 2015 from a large healthcare delivery system in Taiwan. Patients with renal replacement therapy or undergoing ULT for <3 months were excluded. Propensity score-matched cohort study design was conducted to compare outcomes between patients initiated with febuxostat or allopurinol therapy. Cox regression analyses were employed to compare the adjusted hazards ratio (aHR) of incident event of estimated glomerular filtration rate (eGFR) ? 30% decrease, and the difference in longitudinal changes in serum uric acid (SUA) and eGFR between groups was analyzed using linear mixed model. Overall, 1050 CKD patients who initiated febuxostat (n?=?525) or allopurinol (n?=?525) treatment were observed for 2.5 years. Compared with allopurinol, febuxostat use was associated with higher rate of patients maintaining SUA target <6?mg/dL in >80% of follow-up time with a reduction in mean SUA change. There were no significant differences in the mean eGFR changes over time between the febuxostat and allopurinol groups or in the risk of eGFR decline ?30% of baseline. Febuxostat was associated with greater reduction in SUA level than allopurinol in patients with CKD. However, febuxostat and allopurinol showed no difference in renal function changes during study follow-up. These findings require further investigation with long-term follow up in CKD patients with hyperuricemia.

SUBMITTER: Peng YL

PROVIDER: S-EPMC7329906 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease.

Peng Yueh-Lung YL Tain You-Lin YL Lee Chien-Te CT Yang Yi-Hsn YH Huang Yaw-Bin YB Wen Yen-Hsia YH Hsu Chien-Ning CN

Scientific reports 20200701 1

Whether the clinical trial treatment effect of urate-lowering therapy (ULT) in patient with chronic kidney disease (CKD) is generalizable to real-word settings is unclear. This study aimed to compare febuxostat with allopurinol for uric acid reduction and renal protection in patients with CKD. Adult CKD patients newly treated with ULT were identified using electronic health records from 2010 to 2015 from a large healthcare delivery system in Taiwan. Patients with renal replacement therapy or und ...[more]

PMID: 32612180

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Project description:BackgroundThe relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues.MethodsParticipants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events.ResultsThis study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events.ConclusionsAllopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.).

Dataset Information

Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease.

Publications

Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease.

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